A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of Ferritin Nanoparticles Expressing Native-like HIV-1 Envelope Trimers Followed by Boost With mRNA Lipid Nanoparticles Encoding a Native-like HIV-1 Envelope Trimer in Adults Without HIV
概览
- 阶段
- 1 期
- 干预措施
- V3G CH848 mRNA-Tr2 50mcg
- 疾病 / 适应症
- Hiv
- 发起方
- National Institute of Allergy and Infectious Diseases (NIAID)
- 入组人数
- 36
- 试验地点
- 6
- 主要终点
- Local reactogenicity signs and symptoms for a minimum of 14 days following receipt of any study vaccine
- 状态
- 进行中（未招募）
- 最后更新
- 12天前
概览
简要总结
This first-in-human (FIH) phase 1 clinical trial will evaluate a prime-boost regimen of immunogens designed to induce HIV-1 Env V3-glycan-specific broadly neutralizing antibodies (V3G bNAbs). The priming immunogen (V3G CH848 Pr-NP1) consists of ferritin NPs expressing 8 copies of an Env trimer. This immunogen will be boosted with an mRNA LNP (V3G CH848 mRNA-Tr2), encoding a soluble Env trimer which does not utilize the ferritin NP design.
研究者
入排标准
入选标准
- •Able and willing to complete the informed consent process, including an Assessment of Understanding (AoU): Volunteer demonstrates an understanding of this study and completes a questionnaire prior to first vaccination with verbal demonstration of understanding of questionnaire items that were answered incorrectly.
- •18 to 55 years old, inclusive, on day of enrollment.
- •Available for clinic follow-up through the last clinic visit, willing to undergo lymph node fine needle aspiration and leukapheresis, and willing to be contacted 12 months after the last study-product administration.
- •Agrees not to enroll in another study of an investigational agent during participation in the trial. If a potential participant is already enrolled in another clinical trial, approvals from the other trial sponsor and the HVTN 307 PSRT are required prior to enrollment into HVTN
- •In good general health according to the clinical judgment of the site investigator.
- •Physical examination and laboratory results without clinically significant findings that would interfere with assessment of safety or reactogenicity in the clinical judgement of the site investigator.
- •Assessed by clinical staff as having a low likelihood of acquiring HIV per guidelines, agrees to discuss their potential for HIV acquisition, agrees to risk-reduction counseling, and agrees to avoid behaviors associated with a higher likelihood of acquiring HIV through the final study visit. Low likelihood may include persons stably taking pre-exposure prophylaxis (PrEP) as prescribed.
- •Hemoglobin (Hgb):
- •≥ 11.0 g/dL for volunteers AFAB
- •≥ 13.0 g/dL for volunteers AMAB and for volunteers AFAB or intersex at birth who have been on masculinizing hormone therapy for more than 6 consecutive months
排除标准
- •Volunteer who is breastfeeding or pregnant.
- •Body mass index (BMI) ≥
- •Enrollment of individuals with BMI ≥ 40, whom the site investigator assesses are in good health, may be considered by PSRT approval.
- •Diabetes mellitus (DM). Type 2 DM controlled with diet alone (and confirmed by HgbA1c ≤ 8% within the last 6 months) or a history of isolated gestational diabetes are not exclusionary. Enrollment of individuals with Type 2 DM that is well controlled on hypoglycemic agent(s) may be considered by the PSRT on a case-by-case basis, provided that the HgbA1c is ≤ 8% within the last 6 months (sites may draw these at screening).
- •Previous or current recipient of an investigational HIV vaccine (previous placebo/ control recipients are not excluded).
- •Receipt of non-HIV experimental vaccine(s) received within the last 1 year. Exceptions include vaccines that have subsequently undergone licensure or Emergency Use Authorization (EUA) by the FDA or World Health Organization (WHO) emergency use listing (EUL), or if outside the US, by the national Regulatory Authority (RA) authorizing this clinical trial.
- •Congenital or acquired immunodeficiency, including systemic medication use likely to impair immune response to vaccine in the opinion of the site investigator, such as glucocorticoid use, equal to or greater than prednisone 10 mg/day within 3 months prior to enrollment.
- •Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires PSRT approval.
- •Receipt of any of the following within 4 weeks prior to enrollment;
- •Live replicating vaccines
研究组 & 干预措施
Group 1: Low dose V3G CH848 Pr-NP1 with 3M-052-AF + Alum
3 doses of V3G CH848 Pr-NP1 (60 mcg) combined with 3M-052-AF (5 mcg) and Alum (500 mcg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit
干预措施: V3G CH848 mRNA-Tr2 50mcg
Group 2: Low dose V3G CH848 Pr-NP1 with ACU-026-001-1
3 doses of V3G CH848 Pr-NP1 (60 mcg) combined with ACU-026-001-1 (2.0 mg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit
干预措施: V3G CH848 Pr-NP1 60mcg
Group 1: Low dose V3G CH848 Pr-NP1 with 3M-052-AF + Alum
3 doses of V3G CH848 Pr-NP1 (60 mcg) combined with 3M-052-AF (5 mcg) and Alum (500 mcg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit
干预措施: V3G CH848 Pr-NP1 60mcg
Group 1: Low dose V3G CH848 Pr-NP1 with 3M-052-AF + Alum
3 doses of V3G CH848 Pr-NP1 (60 mcg) combined with 3M-052-AF (5 mcg) and Alum (500 mcg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit
干预措施: 3M-052-AF 5mcg
Group 1: Low dose V3G CH848 Pr-NP1 with 3M-052-AF + Alum
3 doses of V3G CH848 Pr-NP1 (60 mcg) combined with 3M-052-AF (5 mcg) and Alum (500 mcg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit
干预措施: Alum 500 mcg
Group 3: V3G CH848 Pr-NP1 with 3M-052-AF + Alum
3 doses of V3G CH848 Pr-NP1 (100 mcg) combined with 3M-052-AF (5 mcg) and Alum (500 mcg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit
干预措施: 3M-052-AF 5mcg
Group 3: V3G CH848 Pr-NP1 with 3M-052-AF + Alum
3 doses of V3G CH848 Pr-NP1 (100 mcg) combined with 3M-052-AF (5 mcg) and Alum (500 mcg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit
干预措施: Alum 500 mcg
Group 2: Low dose V3G CH848 Pr-NP1 with ACU-026-001-1
3 doses of V3G CH848 Pr-NP1 (60 mcg) combined with ACU-026-001-1 (2.0 mg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit
干预措施: V3G CH848 mRNA-Tr2 50mcg
Group 2: Low dose V3G CH848 Pr-NP1 with ACU-026-001-1
3 doses of V3G CH848 Pr-NP1 (60 mcg) combined with ACU-026-001-1 (2.0 mg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit
干预措施: ACU-026-001-1 2.0mg
Group 3: V3G CH848 Pr-NP1 with 3M-052-AF + Alum
3 doses of V3G CH848 Pr-NP1 (100 mcg) combined with 3M-052-AF (5 mcg) and Alum (500 mcg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit
干预措施: V3G CH848 mRNA-Tr2 50mcg
Group 3: V3G CH848 Pr-NP1 with 3M-052-AF + Alum
3 doses of V3G CH848 Pr-NP1 (100 mcg) combined with 3M-052-AF (5 mcg) and Alum (500 mcg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit
干预措施: V3G CH848 Pr-NP1 100mcg
Group 4: V3G CH848 Pr-NP1 with ACU-026-001-1
3 doses of V3G CH848 Pr-NP1 (100 mcg) combined with ACU-026-001-1 (2.0 mg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit
干预措施: V3G CH848 mRNA-Tr2 50mcg
Group 4: V3G CH848 Pr-NP1 with ACU-026-001-1
3 doses of V3G CH848 Pr-NP1 (100 mcg) combined with ACU-026-001-1 (2.0 mg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit
干预措施: ACU-026-001-1 2.0mg
Group 4: V3G CH848 Pr-NP1 with ACU-026-001-1
3 doses of V3G CH848 Pr-NP1 (100 mcg) combined with ACU-026-001-1 (2.0 mg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit
干预措施: V3G CH848 Pr-NP1 100mcg
结局指标
主要结局
Local reactogenicity signs and symptoms for a minimum of 14 days following receipt of any study vaccine
时间窗: 2 weeks following any injection
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 (exceptions apply)
Systemic reactogenicity signs and symptoms for a minimum of 14 days following receipt of any study vaccine.
时间窗: 2 weeks following any injection
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 (exceptions apply)
Number of AESIs (Adverse events of special interest) leading to early participant withdrawal or permanent discontinuation
时间窗: 12 months following receipt of any study product
Number of SAEs (Serious Adverse Events) leading to early participant withdrawal or permanent discontinuation
时间窗: 12 months following receipt of any study product
Frequency of the V3G-specific precursor IgM+ and IgG+ B cells.
时间窗: 2 weeks following injection
Measured by flow cytometry analysis
Number of MAAEs (medically attended adverse event) leading to early participant withdrawal or permanent discontinuation
时间窗: 12 months following receipt of any study product
Number of AEs (adverse events) leading to early participant withdrawal or permanent discontinuation
时间窗: 12 months following receipt of any study product
次要结局
- Magnitude of serum Ab autologous neutralization of vaccine-matched tier 2 HIV-1 strains(2 weeks after the priming regimen and 2 weeks after the boost with V3G CH848 mRNA-Tr2)
- Magnitude of CD4+ T-cell responses(2 weeks after the priming regimen and 2 weeks after the boost with V3G CH848 mRNA-Tr2)
- Response rate of serum Ab autologous neutralization of vaccine-matched tier 2 HIV-1 strains(2 weeks after the priming regimen and 2 weeks after the boost with V3G CH848 mRNA-Tr2)
- Occurrence of CD4+ T-cell responses(2 weeks after the priming regimen and 2 weeks after the boost with V3G CH848 mRNA-Tr2)
- Response rate of CD4+ T-cell responses(2 weeks after the priming regimen and 2 weeks after the boost with V3G CH848 mRNA-Tr2)
- Response rate of serum IgG binding Abs(2 weeks after the priming regimen and 2 weeks after the boost with V3G CH848 mRNA-Tr2)
- Magnitude of serum IgG binding Abs(2 weeks after the priming regimen and 2 weeks after the boost with V3G CH848 mRNA-Tr2)